Patients with DiGeorge syndrome are born with no thymus and no T cells. They die of infection, tumors, or autoimmune disease. We are transplanting these patients with postnatal, cultured, human thymic tissue to test several hypotheses; 1) that host bone marrow stem cells will migrate to the transplanted tissue, 2) that host thymocytes will develop and have a normal phenotype, and 3) that T cell function will develop. We have done three thymic transplants in patients at Duke with complete DiGeorge syndrome. The first Duke transplant was done in September, 1993. This patient developed normal T cell function as measured by mitogen responsiveness, mixed lymphocyte reactions and responses to tetanus. The patient is tolerant of the donor. She makes normal antibodies to tetanus and pneumovax. The thymus transplant was biopsied at 3 months. It showed normal appearing thymic architecture and normal thymocytes which were all host in origin. The patient has been free of infection and been living at home off all medications except calcium since May, 1994. She is developing normally. The second patient was transplanted in July, 1994, with a thymus that was haploidentical with the patient. This patient developed functional T cells (normal responses to PHA) but died after receiving a tracheostomy for laryngomalacia. The thymus transplant of this patient was assessed at autopsy and showed normal appearing epithelium with Hassall's bodies. The third transplant was done at the end of December, 1997. It is too early to assess outcome. This study is important to show that host thymopoiesis can occur after thymic transplantation and thus may aid in T cell immunoreconstitution. This study is a control for research studies of thymic transplantation in HIV infection. Our future plans include transplanting additional patients to determine if the findings in the first two patients can be generalized. If they can, we hope to establish thymic transplantation as an accepted form of immunoreconstitution for these unfortunate patients.